Methods of making bimetal complexes

ABSTRACT

Methods of forming bimetal complexes including reacting polyfunctional compounds with two or more coordination elements and recovering a bimetal complex.

CROSS REFERENCE TO RELATED APPLICATION

This Application is a divisional application of U.S. application Ser.No. 11/668,020 filed Jan. 29, 2007 which is a continuation-in-part ofU.S. application Ser. No. 11/647,623 filed Dec. 29, 2006, now U.S. Pat.No. 7,687,650 which claims priority benefit to U.S. ProvisionalApplication No. 60/764,968 filed Feb. 3, 2006 the entire disclosures ofwhich are incorporated herein by this reference.

BACKGROUND

1. Technical Field

The present disclosure relates compositions that contain bimetalcomplexes. The bimetal complexes can be prepared by reacting apolyfunctional compound with two or more coordination elements.

2. Background of the Invention

Polycarboxylic acids are polyfunctional acids used in many products. Theion form of carboxylic acids, as well as its esters and salts, are knownas carboxylates. Various copper carboxylates are known through theextensive use of the carboxylate ion in crystal engineering to explorethe structural chemistry of copper (II) carboxylates, which exist, forexample as copper (II) malonates, copper (II) coppergiutamates, coppercitrates and other copper complexes known.

However, the study of copper (II) reaction products of polyfunctionalacids and the formation of carboxylates are problematic in that theconditions of synthesis, stoichiometry and temperature should be knownand applied in order to synthesize the desired product. For example, themixture of copper carbonate and malonic acid in a 1:2 molar ratio keptat 5° C. for weeks results in the formation of deep blue copper (II)malonate trihydrate crystals.

It would be desirable to provide compositions containing reactionproducts of polyfunctional carboxylic acid compounds with two or morecoordination elements. For example, it would be desirable to providemalonates having both copper and at least one other metallicconstituent, such as zinc. These can be obtained by reacting a mixtureof malonic and a 3:1:1 molar ratio with the metallic componentsresulting in the formation of greenish-blue copper II zinc II malonatecrystals.

Polyamines are polyfunctional bases used in many products. When combinedwith metallic constituent, the ion form of amines as well as theiramides and salts, can produce amino complexes. Various copper aminecomplexes are used extensively in crystal engineering to explore thestructural chemistry of amine complexes, such as, for example, copper(II) amine complexes. Copper (II) amine complexes exist in numerousforms, many of which have an intense blue color. For example, intenseblue various copper (II) ethylenediamine complexes are known.

However, the study of reaction products of poly-functional amines andthe formation of amine complexes are problematic in that conditions ofsynthesis, stoichiometry and temperature should be known and applied inorder to synthesize the desired product. For example, a mixture ofbutylene diamine, copper chloride, zinc chloride in a 3:1:1 molar ratioresults in the formation of dry, blue crystals.

It would be desirable to provide compositions containing reactionsproducts of polyfunctional amine compounds with two or more coordinationelements. For example, it would be desirable to provide amines complexeshaving both copper and at least one other metallic constituent, such aszinc.

Poly-functional organic compounds having a carboxyl group and an aminegroup are known as amino acids. The ionic form of amino acids vary withthe pH of the media, with ionic forms of the acid being known ascarboxylates and the ionic forms of the amine as being known as ammoniumcomplexes.

Various copper amino acid complexes are known through the extensive useof the amino acids in crystal engineering to explore the structuralchemistry of copper (II) amino acid complexes. They exist in numerousforms such as copper (II) glycinate, copper II glutamate, etc. However,one study of reaction products of polyfunctional amino acids and theformation of amino acid complex is problematic in that conditions ofsynthesis, stoichiometry and temperature should be known and applied inorder to synthesize the desired product.

It would also be desirable to provide compositions containing reactionproducts of amino acid compounds with two or more coordination elements.For example, it would be also desirable to provide amino acid complexeshaving copper and at least one other metallic constituent, such as zinc.For example in a mixture of glutamic acid, zinc carbonate and coppercarbonate in a 3:1:1 molar ratio results in the formation ofgreenish-blue crystals. It would be desirable to provide compositionscontaining reaction products of polyfunctional compounds with two ormore coordination elements. It would also be desirable to provideglutamates having both copper and at least one other metallicconstituent, such as zinc.

SUMMARY

Compositions in accordance with the present disclosure contain a bimetalcomplex. The bimetal complex can be the reaction product of apolyfunctional compound with two or more coordination elements. Thepolyfunctional compound can be, for example, a polyfunctional acid or anamino acid. The coordination elements can be selected from the elementslisted in Groups IIIA to VIIIA, Groups IB to IIIB, of periods 4 and 5and aluminum in Group IIIB, period 3 of The Periodic Table of theElements.

Methods of making such reaction products are also described. Inembodiments, bimetal complexes are made by 1) contacting one or morepolyfunctional compounds with two or more coordination elements, whereinthe molar ratio of polyfunctional compound to two or more coordinationelements is at least 3:2; and 2) isolating the reaction product.

In embodiments, copper-zinc malonate complexes are synthesized frommalonic acid and copper and zinc constituents. Methods of makingcopper-zinc dual salts are also described. In embodiments, copper-zincmalonate compositions are made by:

1) contacting malonic acid with one or more bases containing copper andzinc constituents in an aqueous solution, wherein the molar ratio ofmalonic acid to copper to zinc is about 3:1:1; and 2) recovering thecopper-zinc malonate product.

Excess malonic acid in the manufacturing process may drive the formationof copper-zinc malonates which precipitate in the reaction solution.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS

The preparation of reaction products of polyfunctional compounds withtwo or more coordination elements and compositions containing suchreaction products are described.

The polyfunctional compound can be any compound that contains at leasttwo functional groups that may complex with metal cations in solution.Among the functional groups that may be present include carboxylic acidgroups and amino groups. Suitable polyfunctional compounds include, butare not limited to polyfunctional acids, polyfunctional amines and aminoacids. Other suitable polyfunctional compounds will be readilyenvisioned by those skilled in the art reading the present disclosure.It should of course be understood that mixtures of polyfunctionalcompounds may be used.

Polyfunctional acids are primarily monomeric compositions having two ormore carboxylic acid groups. Non-limiting examples of polyfunctionalacids include maleic acid, fumaric acid, citraconic acid, itaconic acid,glutaconic acid, phthalic acid, isophthalic acid, terephthalic acid,cyclohexane dicarboxylic acid, succinic acid, adipic acid, sebacic acid,azealic acid, malonic acid, dodecanedioic acid, 1,18-octadecanedioicacid, dimer acids (prepared from a mono-, di- or triunsaturated fattyacid, acid wax, acid anhydride grafted wax, or other suitablepolycarboxylic acid reacting compound), alkenyl succinic acids (such asn-dodecenylsuccinic acid, docecylcucinic acid and octadecenylsuccinicacid). The polyfunctional acid can be present in acidic form, anhydrideform, salt form, or mixtures thereof.

Amino acids may also be used as the polyfunctional compound. Amino acidsare known to those skilled in the art and include at least a carboxylicacid functionality and an amino functionality. Suitable amino acidsinclude naturally occurring amino acids and synthetic amino acids.Non-limiting examples of amino acids include, but are not limited to:glycine; aminopolycarboxylic acids (e.g., aspartic acid,β-hydroxyaspartic acid, glutamic acid, β-hydroxyglutamic acid,β-methylaspartic acid, β-methylglutamic acid, β,β-dimethylaspartic acid,γ-hydroxyglutamic acid, β,γ-dihydroxyglutamic acid, β-phenylglutamicacid, γ-methyleneglutamic acid, 3-aminoadipic acid, 2-aminopimelic acid,2-aminosuberic acid and 2-aminosebacic acid); amino acid amides such asglutamine and asparagine; polyamino- or polybasic-monocarboxylic acidssuch as arginine, lysine, β-aminoalanine, γ-aminobutyrine, ornithine,citruline, homoarginine, homocitrulline, hydroxylysine, allohydroxylsineand diaminobutyric acid; other basic amino acid residues such ashistidine; diaminodicarboxylic acids such as α,α′-diaminosuccinic acid,α,α′-diaminoglutaric acid, α,α′-diaminoadipic acid, α,α′-diaminopimelicacid, α,α′-diamino-β-hydroxypimelic acid, α,α′-diaminosuberic acid,α,α′-diaminoazelaic acid, and α,α′-diaminosebacic acid; imino acids suchas proline, hydroxyproline, allohydroxyproline, γ-methylproline,pipecolic acid, 5-hydroxypipecolic acid, and azetidine-2-carboxylicacid; mono- or dialkyl (typically C₁ -C₈ branched or normal) amino acidssuch as alanine, valine, leucine, allylglycine, butyrine, norvaline,norleucine, heptyline, α-methylserine, α-amino-α-methyl-γ-hydroxyvalericacid, α-amino-α-methyl-δ-hydroxyvaleric acid,α-amino-α-methyl-ε-hydroxycaproic acid, isovaline, α-methylglutamicacid, α-aminoisobutyric acid, α-aminodiethylacetic acid,α-aminodiisopropylacetic acid, α-aminodi-n-propylacetic acid,α-aminodiisobutylacetic acid, α-aminodi-n-butylacetic acid,α-aminoethylisopropylacetic acid, α-amino-n-propylacetic acid,aaminodiisoamyacetic acid, α-methylaspartic acid, α-methylglutamic acid,1-aminocyclopropane-1-carboxylic acid, isoleucine, alloisoleucine,tert-leucine, β-methyltryptophan and α-amino-β-ethyl-β-phenylpropionicacid; β-phenylserinyl; aliphatic α-amino-β-hydroxy acids such as serine,β-hydroxyleucine, β-hydroxynorleucine, β-hydroxynorvaline, andα-amino-β-hydroxystearic acid; α-Amino, α-, γ-, δ- or ε-hydroxy acidssuch as homoserine, γ-hydroxynorvaline, δ-hydroxynorvaline andepsilon-hydroxynorleucine residues; canavine and canaline;γ-hydroxyornithine; 2.hexosaminic acids such as D-glucosaminic acid orD-galactosaminic acid; α-Amino-β-thiols such as penicillamine,β-thiolnorvaline or β-thiolbutyrine; other sulfur containing amino acidresidues including cysteine; homocystine, β-phenylmethionine,methionine, S-allyl-L-cysteine sulfoxide, 2-thiolhistidine,cystathionine, and thiol ethers of cysteine or homocysteine;phenylalanine, tryptophan and ring-substituted α amino acids such as thephenyl- or cyclohexylamino acids α-aminophenylacetic acid,aaminocyclohexylacetic acid and α-amino-β-cyclohexylpropionic acid;phenylalanine analogues and derivatives comprising aryl, lower alkyl,hydroxy, guanidino, oxyalkylether, nitro, sulfur or halo-substitutedphenyl (e.g., tyrosine, methyltyrosine and o-chloro-, p-chloro-,3,4-dicloro, o-, m- or p-methyl-, 2,4,6-trimethyl-, 2-ethoxy-5-nitro-,2-hydroxy-5-nitro- and p-nitrophenylalanine); furyl-, thienyl-,pyridyl-, pyrimidinyl-, purinyl- or naphthylalanines; and tryptophananalogues and derivatives including kynurenine, 3-hydroxykynurenine,2-hydroxytryptophan and 4-carboxytryptophan; α-Amino substituted aminoacids including sarcosine (N-methylglycine), N-benzylglycine,N-methylalanine, N-benzylalanine, N-methylphenylalanine,N-benzylphenylalanine, N-methylvaline and N-benzylvaline; and α-Hydroxyand substituted α-hydroxy amino acids including serine, threonine,allothreonine, phosphoserine and phosphothreonine. glycine, alanine,valine, leucine, isoleucine, serine, threonine, cysteine, methionine,glutamic acid, aspartic acid, lysine, hydroxylysine, arginine,histidine, phenylalanine, tyrosine, tryptophan, proline, asparagine,glutamine and hydroxyproline. Aminopolycarboxylic acids, e.g., asparticacid, β-hydroxyaspartic acid, glutamic acid, β-hydroxyglutamic acid,β-methylaspartic acid, β-methylglutamic acid, β,β-dimethylaspartic acid,γ-hydroxyglutamic acid, β,γ-dihydroxyglutamic acid, β-phenylglutamicacid, γ-methyleneglutamic acid, 3-aminoadipic acid, 2-aminopimelic acid,2-aminosuberic acid and 2-aminosebacic acid. Polyaminoacids may also beused provided they form complexes with the coordination elementsemployed.

The polyfunctional compound is reacted with two or more coordinationelements. The coordination elements can be chosen from the elementslisted in Groups IIIA to VIIIA, Groups IB to IIIB, of periods 4 and 5and aluminum in Group IIIB, period 3 of The Periodic Table of theElements. Suitable non-limiting examples of elements listed in group IBof The Periodic Table of Elements include copper, silver, and gold.Suitable non-limiting examples of coordination elements includealuminum, scandium, titanium, vanadium, chromium, manganese, iron,cobalt, nickel, copper, zinc, gallium, yttrium, zirconium, niobium,molybdenum, technetium, ruthenium, rhodium, palladium, silver, cadmium,and indium. Tin may also be used. Those skilled in the are will readilyenvision suitable compounds for providing the coordination elements insolution.

For example, water soluble salts containing the coordination element maybe used. The salts may be organic or inorganic. Suitable water-solublesilver salts include silver nitrate, silver acetate, silver propionate,silver sulfate, silver butyrate, silver isobutyrate, silver benzoate,silver tartrate, silver salicylate, silver malonate, silver succinateand silver lactate. Suitable water-soluble aluminum salts includealuminum potassium sulfate, aluminum chloride, aluminum sodium sulfate,aluminum sodium phosphate, aluminum sulfate, aluminum nitrate, andsodium aluminate. Suitable water-soluble copper salts include coppersulfate, fluoroborate, hydroxide, borate, fluoride, carbonate,oxychloride, formate or acetate. Suitable water-soluble zinc saltsinclude zinc chloride, zinc bromide, zinc iodide, zinc chlorate, zincbromate, zinc chlorite, zinc perchlorate, zinc sulfate, zinc nitrate,zinc nitrite, zinc borate, zinc metaborate, basic zinc borate, zinchexafluorosilicate, zinc hypophosphite, zinc glycerophosphate, zincbichromate, zinc citrate, zinc thionate, zinc dithionate, zinctetrathionate, zinc pentathionate, zinc thiocyanate, zinc benzoate, zincacetate, zinc salicylate, zinc picrate, zinc permanganate, zinc hydrogenphosphate, zinc formate, zinc ethylsulfate and zinc phenolsulfonate.Examples of suitable water soluble nickel salts that may be used includenickel sulfate hexahydrate and nickel chloride hexahydrate. It should beunderstood that the listed salts are only a small portion of the saltssuitable for use in accordance with the present disclosure. For example,inorganic salts are suitable provided that they provide coordinationelement cations when placed in an aqueous solution. Thus, the foregoinglist of salts should be considered a non-limiting, illustrative list.

For carrying out the process, a reaction solution can be prepared bymixing the various ingredients in water. Water in the mixture mayadvantageously be added in limited amounts sufficient to allow thereaction product to precipitate from solution upon formation.Accordingly, the reaction mixture is not so dilute as to prevent productprecipitate formation. Where necessary, mixing and heating can be usedto bring the reactants to 40-100° C. in order to solubilize thereactants. As a result, reactant solubility may be enhanced throughenergy input such as microwave heating or addition of boiling water. Theinput of the energy may take place through any instrument capable ofheating the aqueous reaction mixture. The reaction products formed insolution may be immediately separated so that their production can takeplace in a continuous process. Where a short reaction time and rapidcrystallization of the reaction product occur, the conversion may becarried out continuously, and the recovery of the resultant solidproduct may take place by any conventional manner such as filtering,centrifugation, or sedimentation.

The polyfunctional compound is present in the reaction mixture inamounts that will contact metal cations in an aqueous solution. Suitableamounts of polyfunctional compound also include excess amounts inrelation to the amount of metal cations. In embodiments, polyfunctionalcompound is present in a 3:1:1 molar ratio in relation to the metalconstituents. In embodiments, the polyfunctional compound is malonicacid which can be present in acidic form, salt form, or mixturesthereof. In embodiments, the process parameters are especiallyadvantageous if the polyfunctional compound is added to excess incomparison to the metal counter cation constituents. Depending on thedesired complex, the latter are added so that the molar ratio ofpolyfunctional compound to metal ions is approximately 3:2.

In embodiments, the coordination elements may be present as one or moreionic compounds formed by joining one or more independent coordinationelement molecules or ions of a first type and coordination elementmolecules or ions of a second type to a central unit by ionic bonds. Forexample, the reaction product may be in the form of a trinuclear cation,where structurally independent coordination element hydrates are bridgedby a central unit. However, various coordination modes are possibledepending on the source of the coordination elements and synthesisconditions. In embodiments, the central unit may be a multi-memberedring such as eight-membered ring, six-membered ring, and four-memberedmetalocycle for bridging or chelating functions between the coordinationelement constituents. Accordingly, the crystal structures of thereaction products can be very diverse, from ionic to three-dimensionalpolymers. In embodiments, the reaction products are present in severalhydrate, and polymorphic forms.

In embodiments, suitable reaction products can be non-toxic bimetalcomplexes that include copper, zinc, aluminum and/or silverconstituents. Such copper, zinc, aluminum and/or silver reactionproducts include, but are not limited to water soluble compounds thatcontain copper, zinc, aluminum and/or silver. Non-limiting examples ofwater-soluble bimetal complexes include copper-zinc citrate,copper-silver citrate, silver-zinc citrate, copper-zinc oxalate,copper-silver oxalate, silver-zinc oxalate, copper-zinc tartarate,copper-silver tartarate, silver-zinc tartarate, copper-zinc malate,copper-silver malate, silver-zinc malate, copper-zinc succinate,copper-silver succinate, silver-zinc succinate, copper-zinc malonate,copper-silver malonate, silver-zinc malonate, copper-zinc maleate,copper-silver maleate, silver-zinc maleate, copper-zinc aspartate,copper-silver aspartate, silver-zinc aspartate, copper-zinc glutamate,copper-silver glutamate, silver-zinc glutamate, copper-zinc glutarate,copper-silver glutarate, silver-zinc glutarate, copper-zinc fumarate,copper-silver fumarate, silver-zinc fumarate, copper-zinc glucarate,copper-silver glucarate, silver-zinc glucarate, copper-zinc polyacrylicacid, copper-silver polyacrylic acid, silver-zinc polyacrylic acid, andcombinations thereof. In embodiments, copper, zinc, aluminum and silversalts of organic multi carboxylic acids are suitable for use inaccordance with the present disclosure. In embodiments, suitable saltscan be doped such that the unit cell of the salt has zinc or silverconstituents dispersed therein. Such zinc or silver constituents mayeither substitute another metallic constituent or fill a preexistingvoid in the unit cell.

In embodiments, suitable reaction products can be copper salts havingzinc or silver constituents therein. For example, zinc or silver mayeither substitute a copper constituent or fill a preexisting void in thecopper salt's unit cell. Suitable non-limiting examples of copper saltswhich may be used to form bimetallic complexes include copper (II)malonate and any hydrated form thereof such as copper (II) malonatedihydrate, copper (II) malonate trihydrate, and copper malonatetetrahydrate. Other suitable non-limiting examples of suitable coppersalt active ingredients include copper citrate, copper oxalate, coppertartarate, copper malate, copper succinate, copper malonate, coppermaleate, copper aspartate, copper glutamate, copper glutarate, copperfumarate, copper glucarate, copper polyacrylic acid, and combinationsthereof. In embodiments, suitable copper salts can be doped such thatthe unit cell of the salt has zinc or silver constituents dispersedtherein. Such zinc or silver constituents may either substitute a copperconstituent or fill a preexisting void in the unit cell.

Cu/Zn Malonate Preferred Embodiments

In embodiments, malonic acid may be reacted with salts containing copperand zinc constituents in an aqueous solution. It has been found thatwhere the malonic acid, copper and zinc constituents are present in atleast about a 3:1:1 molar ratio, copper-zinc malonates may be producedin good yield and high crystalline purity.

Malonic acid refers to 1,3-propanedioic acid, a dicarboxylic acid withstructure CH₂(COOH)₂ or:

The ion form of malonic acid, as well as its esters and salts, are knownas malonates. For example, diethyl malonate is ethyl ester of malonicacid. As used herein, the term copper-zinc malonate applies to any saltsubstances formed from malonic acid having copper and zinc constituents.

Suitable ingredients for the formation of copper-zinc malonates includemalonic acid, one or more bases of copper and zinc, and water. In anaqueous reaction solution, suitable salt forms provide copper and zinccations capable of bonding to malonate anions. Other suitableingredients for the formation of copper-zinc malonates will include thereplacement of bases of copper and zinc with the metallic form of copperand zinc. The elemental form of copper and zinc are known as copper andzinc metals and will be dissolved in the acidic water media as theyreact with malonic acid.

One or more salts containing copper and zinc constituents are present inamounts that will contact malonic acid in an aqueous solution. Suitablesalts for making copper-zinc malonate compositions in accordance withthis disclosure include metal salts containing complex-forming metalions of copper and/or zinc. Non-limiting examples of suitable metalsalts are copper (I) and (II) salts such as copper chloride, copperbromide, copper fluoride, copper nitrate, copper fluoroborate, coppersulfate, copper acetate, copper trifluoro acetate, copper stearate,copper octoate, copper methacrylate, copper malonate, copper benzoate;zinc salts such as zinc bromide, zinc chromate, zinc chloride, zincstearate, zinc octoate, and zinc ethylhexoate. In embodiments, theaqueous solution may include one or more metallic salts, such as cupriccarbonate (CuCO₃.Cu(OH)₂), zinc carbonate (3Zn(OH)₂.2ZnCO₃), metalliccopper, metallic zinc and combinations thereof. Basic salts such asbasic zinc salts, basic copper salts, and combinations thereof are alsosuitable for use in accordance with the present disclosure. Inembodiments, suitable metal basic salts are: copper (I) and (II) saltssuch as copper carbonate, copper oxide, and copper hydroxide; and zincsalts such as zinc carbonate, zinc oxide, and zinc hydroxide.

It should be understood that the listed salts are only a small portionof the salts suitable for use in accordance with the present disclosure.For example, inorganic salts are suitable provided that they providecopper and zinc cations when placed in an aqueous solution. Thus, theforegoing list of salts should be considered a non-limiting,illustrative list.

For carrying out the process, the reaction solution can be prepared bymixing the various ingredients in water where malonic acid and the saltsmay ionize and become more reactive. Water in the mixture is added inlimited amounts sufficient to allow copper-zinc malonates to precipitatefrom solution upon formation. Accordingly, the reaction mixture is notso dilute as to prevent product precipitate formation. Where copper andzinc salts in the reaction mixture are insoluble and form dispersions(such as at cooler temperatures), mixing and heating steps can beapplied to bring the reactants to 40-100° C. in order to solubilize thereactants. As a result, reactant solubility may be enhanced throughenergy input such as microwave heating or addition of boiling waterdissolver. The input of the energy may take place through any instrumentcapable of heating the aqueous reaction mixture. The copper-zincmalonate complexes formed in solution may be immediately separated sothat their production can take place in a continuous process. Due to theshort reaction time and the rapid crystallization of the copper-zincmalonate product, the conversion may be carried out continuously, andthe recovery of the resultant solid product may take place by anyconventional manner such as filtering, centrifugation, or sedimentation.

In the production of the reaction mixture, the concentration of thepolyfunctional compound and that of the copper and zinc constituents maybe pre-selected so that the total concentration of product formedexceeds the solubility equilibrium. This will result in productprecipitating from solution in solid form for easy collection.

In embodiments, the final composition may be a deep blue crystal havinggood yield and substantial crystalline purity. Suitable copper-zincmalonate forms in accordance with the present disclosure include anysalt formed from the neutralization of malonic acid by one or morecopper containing molecules and one or more zinc containing molecules.Illustrative examples include salt formed by the neutralization ofmalonic acid by cupric carbonate (CuCO₃.Cu(OH)₂), and zinc carbonate(3Zn(OH)₂.2ZnCO₃) in an aqueous solution. Here copper may be addedfirst, followed by zinc in order to obtain the salts of the presentdisclosure.

In embodiments, the copper-zinc malonates may be one or more ioniccompounds formed by joining one or more independent copper molecules orions and one or more independent zinc molecules or ions to a centralunit by ionic bonds. For example, the copper-zinc malonate may be in theform of a trinuclear cation, where structurally independent copper andzinc hydrates are bridged by a central unit such as an octahedraldiaquadimalonatocopper (II) unit. However, various coordination modesare possible depending on the source of the copper and zinc andsynthesis conditions. In embodiments, the central unit malonate ion maybe a multi-membered ring such as eight-membered ring, six-membered ring,and four-membered metalocycle for bridging or chelating functionsbetween the copper and zinc constituents. Accordingly, the crystalstructures of copper-zinc malonates can be very diverse, from ionic tothree-dimensional polymers. In embodiments, the copper-zinc malonatescan be found in several hydrate, and polymorphic forms.

In embodiments, the process parameters are especially advantageous ifthe polyfunctional compound is added to excess in comparison to themetal counter cation constituents. Depending on the desired complex, thelatter are added so that the molar ratio of polyfunctional compound tometal ions is approximately 3:2.

Embodiments of Compositions Containing the Reaction Products

In embodiments, the resulting reaction products may serve as activeingredients in compositions suitable for contact with a subject. Suchactive ingredients may be combined with numerous ingredients to formproducts of numerous chemical applications, such as catalytical agents,crosslinking of polymers, superconducting electrical materials,pharmaceutical drugs, food supplements, etc. The active ingredients insuitable toxicological compositions can be applied to the skin, or othertissues of humans or other mammals. Such products may include adermatologically or pharmaceutically acceptable carrier, vehicle ormedium, for example, a carrier, vehicle or medium that is compatiblewith the tissues to which they will be applied. The term“dermatologically or pharmaceutically acceptable,” as used herein, meansthat the compositions or components thereof so described are suitablefor use in contact with these tissues or for use in patients in generalwithout undue toxicity, incompatibility, instability, allergic response,and the like. In embodiments, compositions in accordance with thepresent disclosure can contain any ingredient conventionally used incosmetics and/or dermatology. In embodiments, active ingredients may beformulated to provide crystals in solution, as well as solid forms.

In embodiments, products containing a reaction product in accordancewith the present disclosure as an active ingredient can be in the formof solutions, emulsions (including microemulsions), suspensions, creams,lotions, gels, powders, or other typical solid or liquid compositionsused for treatment of age related skin conditions. Such compositions maycontain, in addition to the reaction product in accordance with thisdisclosure, other ingredients typically used in such products, such asantimicrobials, moisturizers and hydration agents, penetration agents,preservatives, emulsifiers, natural or synthetic oils, solvents,surfactants, detergents, gelling agents, emollients, antioxidants,fragrances, fillers, thickeners, waxes, odor absorbers, dyestuffs,coloring agents, powders, viscosity-controlling agents and water, andoptionally including anesthetics, anti-itch actives, botanical extracts,conditioning agents, darkening or lightening agents, glitter,humectants, mica, minerals, polyphenols, silicones or derivativesthereof, sunblocks, vitamins, and phytomedicinals.

As an illustrative example, products can be formulated to containcopper-zinc malonate in amounts from about 0.001 to about 5% by weightof the total composition. In embodiments, products can be formulated tocontain copper-zinc malonate in an amount from about 0.05 to about 1.0%by weight of the total composition. In other embodiments, the amount ofcopper-zinc malonate is from about 0.1 to about 0.5% by weight of thetotal composition. Here, the copper-zinc malonate present may be in apharmaceutically acceptable salt form. Other active ingredients may beprovided in the formulations at the same concentrations.

In embodiments, compositions in accordance with the present disclosurecan be topically applied to skin in need of improvement such as thereduction or elimination of an undesirable dermatological condition. Asused herein the word “treat,” “treating” or “treatment” refers to usingthe actives or compositions of the present disclosure prophylacticallyto prevent outbreaks of undesirable dermatological conditions, ortherapeutically to ameliorate an existing dermatological condition,and/or extend the duration of the aesthetic benefit of a skin procedure.A number of different treatments are now possible, which reduce and/oreliminate undesirable skin conditions.

As used herein “undesirable skin condition” refers to any skin conditionthat may require treatment of any sort, including skin having one ormore undesirable appearances and/or disagreeable tactile sensations. Theterm further refers to any cosmetically undesirable skin condition, aswell as any undesirable diseased or damaged skin condition.

Non-limiting examples of undesirable skin conditions which can betreated with the topical application of compositions in accordance withthe present disclosure include: acne vulgaris (pimples); atopicdermatitis; birthmarks; cafe-au-laits spots; common benign skin tumorsor growths; common diseases of the nail such as nail infections causedby bacteria, fungi, yeast and/or virus; paronychia; nail disorder due toskin disease such as psoriasis, and/or nail injury; common skinconditions around the eyes such as eyelid contact dermatitis, atopicdermatitis, bacterial skin infection (impetigo or conjunctivitis),xanthelasma, syringoma, skin tags, milia, Naevus, and/or portwinestains; common skin condition associated with housework such as irritantcontact dermatitis, allergic contact dermatitis, contact urticaria,fungal infections, paronychia, and/or viral warts; common diseases ofthe scalp such as seborrhoeic dermatitis, psoriasis of the scalp, lichenplanus, discoid lupus erythematosus (DLE), alopecia areata, seborrhoeickeratoses (seborrhoeic warts, age spots), solar keratoses, angiosarcoma,fungal infection (ringworm, tinea Capitis), bacteria infections of thehair follicles (folliculitis, boils), and/or shingles (Herpes Zoster);common diseases in children such as atopic dermatitis, atopic eczema,discoid eczema, pityriasis alba, vitiligo, and/or alopecia areata;common diseases of the mouth and lips such as oral candidiasis, oralleukoplakia, apthous ulcers, and/or oral lichen planus; common skinproblems in elderly such as appearance and texture changes, senilepurpura, xerosis/asteatotic eczema, skin Infections/infestations,pigmentary changes, blistering disorders, non-cancerous skin growths,cancerous skin growths, adverse drug reaction, and/or stasis dermatitis;common viral warts; contact allergy; diaper candidiasis, drug allergy,folliculitis; freckles; fungal infections of the skin such as whitespot, athlete's foot, jock itch, and/or moniliasis/candidiasis; guttatehypomelanosis; hair loss; hand eczema; impetigo; lines, crow's feet,wrinkles, etc.; melasma; molluscum contagiosum; occupational skindisease such as irritation and/or allergy; post-Inflammatorypigmentation; psoriasis; rosacea; shingles; skin cancers; skin diseasesin diabetes mellitus; skin diseases in pregnancy; skin disorders causedby cosmetics such as irritant contact dermatitis and/or allergic contactdermatitis, cosmetic induced pimples (acne), sunscreens allergy, and/orspecial cosmetic allergies, solar lentigenes; tinea capitis; viralwarts; vitiligo; and combinations of these undesirable skin conditions.

In embodiments, compositions in accordance with the present disclosureare suitable for treating diseased skin, or any condition which canresult from the excessive amount of pathogens such as fungi, viruses,and or bacterium affecting the skin in any way.

In embodiments, an undesirable skin condition is skin that has a roughtexture or uneven appearance such as psoriasis, bumps, razor burns,and/or patches.

The particular active ingredient or ingredients employed, and theconcentration in the compositions, generally depends on the purpose forwhich the composition is to be applied. For example, the dosage andfrequency of application can vary depending upon the type and severityof the skin condition.

Treatments in accordance with the present disclosure contact skin withone or more active ingredients such as those containing copper, zincand/or silver in an effective amount to improve the undesirable skinconditions. In embodiments, patients are treated by topically applyingto skin suffering a condition, one or more copper-zinc malonates. Inembodiments, patients are treated by topically applying to skinsuffering from a condition, one or more salts in accordance with thepresent disclosure. The active ingredient is applied until the treatmentgoals are obtained. However, the duration of the treatment can verydepending on the severity of the condition. For example, treatments canlast several weeks to months depending on whether the goal of treatmentis to reduce or eliminate the skin condition.

In treatment embodiments, the compositions and methods in accordancewith the present disclosure can be combined with other skin treatmentsystems. For example, the bimetallic salt complexes and be applied toskin in combination with skin treatment systems such as the ObagiNuDerm® skin treatment system and related Obagi skin care products fromO.M.P. Inc. of Long Beach Calif. More specifically copper-zinc malonatecompositions can be combined with the Obagi Nuderm® skin treatmentsystem in order to promote the beneficial affects of that system. Theactive ingredients and formulations in accordance with the presentdisclosure may either be incorporated into other product formulations,or applied to the skin before, after, and/or during other skintreatments.

In embodiments, the compositions may contain any active ingredient or beformulated and applied as described in commonly owned U.S. PatentApplication entitled Anti-aging Treatment Using Copper-Zinc Compositions(U.S. Ser. No. 11/452,642 filed Jun. 14, 2006) herein incorporated byreference in its entirety.

The following non-limiting examples further illustrate compositions andmethods in accordance with this disclosure.

EXAMPLE 1

Example 1 below shows suitable ingredients of a reaction mixture forforming copper-zinc malonates in accordance with the present disclosure.

Ingredient Amount Malonic acid 1.8 g cupric carbonate 0.632 g zinccarbonate 0.626 g Water 100 ml

EXAMPLE 2

1.8 g of malonic acid (CH₂(COOH)₂) was combined with 0.632 grams ofcupric carbonate (CuCO₃.Cu(OH)₂), 0.626 g of zinc carbonate(3Zn(OH)₂.2ZnCO₃) , and 100 ml of water to form a dispersion. Thesolution was heated until the reactants went into solution. Well-defineddeep-blue crystals precipitated and were separated from the aqueoussolution of malonic acid, cupric carbonate, and zinc carbonate (3:1:1molar ratio) that had been kept at room temperature. Dual salt wasformed by replacing acid groups with copper and zinc cations in the samemolecule. The deep blue crystals were found to have a melting point ofabout 210° C.

Sample prepared as per ASTM-D-1971-95 (herein incorporated by referencein its entirety) and analyzed by method 6010 (I.C.P.) (hereinincorporated by reference in its entirety) showed 16.5% copper and 12.4%zinc.

EXAMPLE 3

1.8 g of malonic acid (CH₂(COOH)₂) was combined with 0.632 grams ofcupric carbonate (CuCO₃.Cu(OH)₂), 0.626 g of zinc carbonate(3Zn(OH)₂.2ZnCO₃) , and 100 ml of boiling water. Well-defined deep-bluecrystals were separated from the aqueous solution of malonic acid,cupric carbonate, and zinc carbonate (3:1:1 molar ratio) that had beenkept at room temperature for 1 week.

EXAMPLE 4

3 moles of malonic acid is thoroughly mixed with 1 mole of copper ascupric carbonate and 1 mole of zinc as zinc carbonate in a stirred tankreactor containing 100 ml of heated water (approximately 95-100° C.).After a short reaction time, copper-zinc malonate precipitates out ofsolution with a high yield. A filtration step is used to isolate thecomplex as a powder. Deep blue crystals are obtained having a meltingpoint of about 210° C.

EXAMPLE 5

In embodiments, copper-zinc malonate formulations have the followingmake-up:

COMPONENT % BY WEIGHT Copper-zinc malonate* 0.1% (Active ingredient)Glycerine 3.0% Propylene Glycol 25.0% Distilled Water 71.9%

EXAMPLE 6

A 72 year old woman is suffering from wrinkling on her face. Thecomposition of example 5 suitable for treatment of skin containing aneffective amount of copper-zinc malonate active ingredient is routinelyapplied to her face twice daily. Wrinkling is reduced or eliminated.

EXAMPLE 7

3 moles of glutamic acid is thoroughly mixed with 1 mole of copper ascupric carbonate and 1 mole of zinc as zinc carbonate in a stirred tankreactor containing 100 ml of heated water (approximately 95-100° C.).After a short reaction time, copper-zinc glutamate precipitates out ofsolution with a high yield. A filtration step is used to isolate thecomplex as a powder.

While several embodiments of the disclosure have been described, it isnot intended that the disclosure be limited thereto, as it is intendedthat the disclosure be as broad in scope as the art will allow and thatthe specification be read likewise. Therefore, the above descriptionshould not be construed as limiting, but merely as exemplifications ofembodiments. Those skilled in the art will envision other modificationswithin the scope and spirit of the claims appended hereto.

1. A method of forming a bimetal complex comprising dissolving an aminoacid having at least two carboxylic acid groups in a solvent to form asolution; adding a source of a first coordination element to thesolution; adding a source of a second coordination element to thesolution, wherein the first coordination element is different from thesecond coordination element and the first and second coordinationelements are individually selected from copper, silver, gold, aluminum,scandium, titanium, vanadium, chromium, manganese, iron, cobalt, nickel,copper, zinc, gallium, yttrium, zirconium, niobium, molybdenum,technetium, ruthenium, rhodium, palladium, silver, cadmium, indium andtin; and recovering a bimetal complex.
 2. A method as in claim 1 whereinthe coordination first and second elements are copper and zinc,respectively.
 3. A method as in claim 1 wherein the source of a firstcoordination element provides Cu⁺² ions in the solution.
 4. A method asin claim 1 wherein the source of a second coordination element providesZn⁺² ions in the solution.
 5. A method as in claim 1 wherein the sourceof a first coordination element and the source of a second coordinationelement provides, respectively, are compounds of the formulaCu(O₂C—CH₂CO₂)₂ and Zn(O₂C—CH₂CO₂)₂.
 6. A method as in claim 1 whereinthe amino acid having at least two carboxylic acid groups is a glutamicacid or an aspartic acid.
 7. A method of forming a bimetal complexcomprising dissolving a polyamine in a solvent to form a solution;adding a source of a first coordination element to the solution; addinga source of a second coordination element to the solution, wherein thefirst coordination element is different from the second coordinationelement and the first and second coordination elements are individuallyselected from copper, silver, gold, aluminum, scandium, titanium,vanadium, chromium, manganese, iron, cobalt, nickel, copper, zinc,gallium, yttrium, zirconium, niobium, molybdenum, technetium, ruthenium,rhodium, palladium, silver, cadmium, indium and tin; and recovering abimetal complex.
 8. A method as in claim 7 wherein the coordinationfirst and second elements are copper and zinc, respectively.
 9. A methodas in claim 7 wherein the source of a first coordination elementprovides Cu⁺² ions in the solution.
 10. A method as in claim 7 whereinthe source of a second coordination element provides Zn⁺² ions in thesolution.
 11. A method as in claim 7 wherein the source of a firstcoordination element and the source of a second coordination elementprovides, respectively, are compounds of the formula Cu(O₂C—CH₂CO₂)₂ andZn(O₂C—CH₂CO₂)₂.